Apparatus and method for preparation of a peritoneal dialysis solution

ABSTRACT

The invention provides an apparatus and method for storing and transporting peritoneal dialysate in dry or lyophilized form, and for forming a deliverable peritoneal dialysis solution therefrom. In one embodiment, a dry reagent bed, including reagents sufficient to produce a dialysis solution, is suspended in a diluent flow path through the apparatus housing. Continuous pressure on the reagent bed causes the bed to compact as it erodes when purified water is passed through the housing. The pressure ensures complete and even dissolution of the reagents. Through dry storage and simple dissolution, even in a home, the invention enables a wider variety of solution constituents, including reduced acid content and the use of bicarbonate as a stable buffer component. The latter is illustrated in a double-bed embodiment, where bicarbonate is stored separately from calcium or magnesium salts within a single housing.

RELATED APPLICATION

[0001] This application is a continuation of co-pending U.S. patentapplication Ser. No. 09/908,785, now U.S. Pat. No. 6,426,056, which is acontinuation of U.S. patent application Ser. No. 09/227,448, filed onMar. 26, 1999, now U.S. Pat. No. 6,274,103, both of which are herebyincorporated by reference in their entirety.

FIELD OF THE INVENTION

[0002] The invention generally relates to peritoneal dialysis, and moreparticularly to devices and methods for producing a peritoneal dialysissolution from dry reagents.

BACKGROUND OF THE INVENTION

[0003] Treatments for patients having substantially impaired renalfunction, or kidney failure, are known as “dialysis.” Either blooddialysis (“hemodialysis”) or peritoneal dialysis methods may beemployed. Both methods essentially involve the removal of toxins frombody fluids by diffusion of the toxins from the body fluids into a toxinfree dialysis solution.

[0004] Hemodialysis involves removing blood from the patient,circulating the blood through a dialysis machine outside the body, andreturning the blood to the patient. As the blood is directly in contactwith the hemodialysis membrane, the patient ordinarily needs to betreated only 3-5 hours at a time, about three times per week.Unfortunately, hemodialysis requires the use of complex and expensiveequipment, and can therefore normally only be performed under controlledconditions of a hospital or other specialized clinic.

[0005] Peritoneal dialysis, on the other hand, can be performed wheresuch complex equipment is not readily available, such as in thepatient's home. In the peritoneal dialysis process, the patient'speritoneal cavity is filled with a dialysate solution. Dialysates areformulated with a high concentration of the dextrose, as compared tobody fluids, resulting in an osmotic gradient within the peritonealcavity. The effect of this gradient is to cause body fluids, includingimpurities, to pass through the peritoneal membrane and mix with thedialysate. By flushing the dialysate from the cavity, the impurities canbe removed.

[0006] Due to indirect contact with bodily fluids through bodilytissues, rather than direct contact with blood, the dextroseconcentration needs to be considerably higher in peritoneal dialysisthan in hemodialysis, and the treatment is generally more prolonged.Peritoneal dialysis may be performed intermittently or continuously. Inan intermittent peritoneal dialysis (IPD) procedure, the patientcommonly receives two liters of dialysate at a time. For example, in acontinuous ambulatory peritoneal dialysis (CAPD) procedure, theperitoneal cavity is filled with two liters of dialysate and the patientis the free to move about while diffusion carries toxins into theperitoneal cavity. After about 4-6 hours, the peritoneum is drained oftoxified dialysate over the course of an hour. This process is repeatedtwo to three times per day each day of the week. Continuous CyclePeritoneal Dialysis (CCPD) in contrast, involves continuously feedingand flushing dialysate solution through the peritoneal cavity, typicallyas the patient sleeps.

[0007] Because peritoneal dialysates are administered directly into thepatient's body, it is important that the dialysis solution maintains thecorrect proportions and concentrations of reagents. Moreover, it isimpractical to formulate and mix dialysis solutions on site at thetypical location of administration, such as the patient's home.Accordingly, peritoneal dialysates are typically delivered to the siteof administration in pre-mixed solutions.

[0008] Unfortunately, dialysis solutions are not stable in solutionsover time. For example, dextrose has a tendency to caramelize insolution over time, particularly in the concentrations required in theperitoneal dialysis context. To prevent such caramelization, peritonealdialysis solutions are typically acidified, such as with hydrochloricacid, lactate or acetate, to a pH between 4.0 and 6.5. The ideal pHlevel for a peritoneal dialysate, however, is between 7.2 and 7.4. Whileachieving the desired goal of stabilizing dextrose in solution, the pHof acidified peritoneal dialysis solutions tends to damage the body'snatural membranes after extended periods of dialysis. Additionally, theuse of acidified peritoneal dialysates tends to induce acidosis in thepatient.

[0009] Bicarbonates introduce further instability to dialysis solutions.The most physiologically compatible buffer for a peritoneal dialysate isbicarbonate. Bicarbonate ions react undesirably with other reagentscommonly included in dialysate solutions, such as calcium or magnesiumin solution, precipitating out of solution as insoluble calciumcarbonate or magnesium carbonate. These insolubles can form even whenthe reactants are in dry form. When occurring in solution, the reactionsalso alter the pH balance of the solution through the liberation ofcarbon dioxide (CO₂). Even in the absence of calcium or magnesium salts,dissolved sodium bicarbonate can spontaneously decompose into sodiumcarbonate and CO₂, undesirably lowering the solution's pH level.

[0010] The current alternatives to bicarbonate for buffering peritonealdialysate are acetate and lactate, but these reagents also haveundesirable chemical consequences. For example, there is some evidencethat acetate may reduce osmotic ultrafiltration and may induce fibrosisof the peritoneal membrane.

[0011] The incompatibility of reagents commonly found in dialysates thuscreates significant logistical problems in connection with theirpreparation, storage and transportation. Attempted solutions to theseproblems have included various devices and methods for providing dryformulations of reagents, and for separately storing and dissolvingincompatible reagents. See, e.g., U.S. Pat. Nos. 4,467,588, 4,548,606,4,756,838, 4,784,495, 5,344,231 and 5,511,875. Many of these proposedsystems involve elaborate water pumping and re-circulation systems, pHand conductivity monitors and water heating components. Moreover,sterile water must be provided independently, further complicating theformulation process.

[0012] While many prior methods and devices have been successful to onedegree or another in addressing logistical problems, they have provenunsatisfactory for various reasons. Conventional systems are quitecomplex and expensive, such that they are impractical for many settings.Thus, dialysate solutions still tend to be prepared well in advance ofadministration, risking destabilization and/or requiring acidificationof the solutions, as noted above. Additionally, pre-formulated solutionsare quite bulky and involve considerable transportation and storageexpense.

[0013] Accordingly, a need exists for improved methods and devices forformulating solutions for peritoneal dialysis. Desirably, such methodsand devices should avoid the problems of non-physiologic solutions andincompatibility of dialysate reagents, and also simplify transportation,storage and mixing of such dialysates.

SUMMARY OF THE INVENTION

[0014] In satisfying the aforementioned needs, the present inventionprovides an apparatus and method for producing dialysis solutions fromdry reagents immediately prior to administration. The invention therebyallow production of physiologically compatible dialysate solutions andminimizes the likelihood of undesirable reactions among reagents.Moreover, the invention facilitates separation of incompatible reagents.Both of these features, independently and in combination, result in arelatively simple and inexpensive apparatus for storing, transportingand producing solution from peritoneal dialysis reagents in dry form.Moreover, the devices and methods expand options for practicallyapplicable solution formulations.

[0015] In accordance with one aspect of the present invention, forexample, an apparatus is provided for producing a peritoneal dialysissolution. The apparatus includes a housing, which defines a fluid flowpath through it. At least one reagent bed is kept within the housingalong the fluid flow path. The reagent bed includes dry reagents inproportions suitable for peritoneal dialysis.

[0016] In accordance with another aspect of the invention, an apparatusproduces a complete peritoneal dialysis solution. The apparatus includesa first dry reagent bed and a second dry reagent bed, which is spacedfrom the first reagent bed. Additionally, the apparatus includes meansfor compressing the first and second reagent beds.

[0017] In accordance with another aspect of the invention, an apparatusis provided for producing a peritoneal dialysis solution from dryreagents. The apparatus includes a housing with a first reagent beddisposed within the housing. The first reagent bed includes a pluralityof chemically compatible reagents. A second reagent bed is also disposedwithin the housing, spaced from the first reagent bed. The secondreagent bed includes a reagent that is chemically incompatible with atleast one of the plurality of reagents of the first reagent bed.Additionally, a first compression component is disposed within thehousing upstream of the first reagent bed, while a second compressioncomponent is disposed within the housing between the first and secondreagent beds. A third compression component is disposed within thehousing downstream of the second reagent bed.

[0018] In accordance with still another aspect of the invention, asystem is provided for producing a peritoneal dialysis solution. Areagent cartridge houses at least one dry reagent bed and at least onecompression component, which exerts continual pressure on the reagentbed. A water purification pack is configured to connect upstream of thereagent cartridge. The water purification pack houses filters, activatedcarbon and ion exhange resins such as to convert potable water toinjectable quality water.

[0019] In accordance with still another aspect of the invention, amethod is provided for producing a peritoneal dialysis solution. Diluentpasses through a dry reagent bed, thereby consuming reagents in the bed.The diluent then carries the consumed reagents out of the bed. Thereagent bed is compacted as the reagents are consumed.

[0020] In accordance with still another aspect of the invention, amethod is disclosed for producing a peritoneal dialysis solution frompurified water. Purified water passes into a reagent cartridge housing,which contains dry reagents sufficient to produce a complete peritonealdialysis solution. The reagents dissolve in the purified water as itpasses through the reagent cartridge.

BRIEF DESCRIPTION OF THE DRAWINGS

[0021] These and other aspects of the invention will be apparent to theskilled artisan in view of the Detailed Description and claims set forthbelow, and in view of the appended drawings, which are meant toillustrate and not to limit the invention, and wherein:

[0022]FIG. 1 is a schematic side perspective view of a system forproducing peritoneal dialysate, constructed in accordance with oneaspect of the present invention.

[0023]FIG. 2 is a schematic side sectional view of a water purificationpack, constructed in accordance with the preferred embodiments.

[0024]FIG. 3 is a schematic side sectional view of a reagent cartridgefor housing reagents of peritoneal dialysate, constructed in accordancewith a preferred embodiment of the present invention.

[0025]FIG. 4 shows the reagent cartridge of FIG. 3 after partialdissolution of the reagents housed therein.

[0026]FIG. 5 shows the reagent cartridge of FIG. 3 after completedissolution of the reagents housed therein.

[0027]FIG. 6 is a schematic side sectional view of a reagent cartridgefor housing reagents of peritoneal dialysate, constructed in accordancewith another preferred embodiment of the present invention.

[0028]FIG. 7 shows the reagent cartridge of FIG. 6 after completedissolution of the reagents housed therein.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

[0029] While the illustrated embodiments are described in the context ofparticular formulations and relative proportions of reagents, theskilled artisan will find application for the described methods anddevices in a variety of different formulations and proportions ofreagents.

[0030] System for Preparing Peritoneal Dialysis Solution

[0031]FIG. 1 illustrates a system 10 for producing solutions suitablefor peritoneal dialysis. As illustrated, a purified diluent source 12 isconnected upstream of a reagent cartridge 14. The cartridge 14, in turn,is in fluid communication with a dialysate reservoir 16 via a tube 18.As set forth in more detail below, purified diluent is provided from thesource 12 to the reagent cartridge 14, wherein the dry reagents aredissolved and peritoneal dialysis solution is delivered to the reservoir16. Alternatively, the solution can be delivered directly to theperitoneal cavity. Advantageously, the solution can be so formedimmediately prior to delivery to the patient's peritoneal cavity, suchthat the dialysate need not be stored in solution form for extendedperiods, and little opportunity exists undesirable reactions within thesolution prior to delivery.

[0032] The cartridge 14 advantageously houses dry or lyophilizedformulations of reagents suitable for peritoneal dialysis. The cartridge14 also defines fluid flow paths through the dry reagents, by way ofporous elements therebetween, enabling dry storage in confined reagentbeds while also enabling dissolution simply by passing diluent throughthe housing. Two preferred versions of the cartridge 14 are described inmore detail with respect to FIGS. 3-7, below.

[0033] In the illustrated embodiment, the diluent source 12 comprises awater purification pack capable of on-site purification of locallyavailable water, such as tap water from a municipal water source. Thepreferred water purification pack is described in more detail withrespect to FIG. 2 below. It will be understood, however, that theskilled artisan will find application for the illustrated reagentcartridge 14 with or without the preferred purification pack. Forexample, the purified diluent source 12 in other arrangements cancomprise a store of pre-sterilized water.

[0034] Water Purification Pack

[0035] Referring to FIG. 2, the preferred purified diluent source 12comprises a fluid purification pack, capable of instantaneouslypurifying water or other diluent to the standards required for injectioninto a patient, and particularly for peritoneal dialysis applications.Advantageously, available water (e.g., tap water) can be introduced tothe system, water is purified as it travels through the pack, and thepurified water is delivered directly to the reagent cartridge 14 (FIG.1). Accordingly, storage of bulky purified water and complex machineryfor purifying water is obviated.

[0036] Conventionally, purifying non-sterile water to the qualitystandards required for use as a diluent for introduction into the humanbody requires extensive mechanical filtration, pumping, distribution andmonitoring systems. These complex mechanisms are eliminated in thepreferred embodiment of the present invention by purifying water throughthe purification pack of FIG. 2. This compact, lightweight pack iscapable of purifying water, at the point of administration, incompliance with the water quality standards set forth in the U.S.Pharmacopoeia for “Sterile Water for Injection.”

[0037] In the illustrated embodiment, the water purification pack 12comprises a housing 20 with an axial inlet 22 and outlet 24. The housingis preferably formed of a suitable polymer, particularly polycarbonate,which aids in purifying water by binding endotoxins through chargeinteractions.

[0038] Immediately downstream of the housing inlet 22 is a depth filter26. The depth filter retains insoluble particulates and microbes greaterthan the pore size of this component. The porosity of the illustrateddepth filter 26 is preferably from 1 to 10 microns, most preferablyabout 1 micron. The depth filter 26 is preferably formed of a porouspolypropylene mesh in multiple layers, particularly 2-3 layers in theillustrated embodiment. Alternatively, the commercially availablecellulose-based depth filters can be employed, as will be understood byone of ordinary skill in the art.

[0039] Downstream of the depth filter 26 is a bed of granular carbon 28.This component removes certain residual organic contaminants, such asendotoxins, as well as commonly used additives placed in the municipallytreated waters (e.g., chlorine, trihalomethanes and chloramine).

[0040] Adjacent to the downstream end of the granular carbon bed 28 is acarbon bed restraint 30. The restraint 30 is a filter of controlledporosity, preferably also comprising a polypropylene mesh with aporosity of about 1-10 microns, more preferably about 1 micron. Thiscomponent prevents passage of particulates shed by the granular carbonbed 28, as well as providing a secondary assurance that insolubleparticulates do not pass further through the water purification pack.

[0041] Adjacent to the downstream side of the carbon bed restraint 30 isa bed 32 of deionization resin beads. The resin bed 32 comprises amixture of pharmaceutical grade resins with strong anion exchanger andstrong cation exchanger chemistries, binding dissociable ions and othercharged particles with a very high affinity. Such resins are available,for example, from Rohm & Haas of Philadelphia, Pa. under the trade nameIRN 150, or from Sybron of Birmingham, N.J. under the trade name NM60.The resin bed 32 also retains endotoxins which escape the upstreamfiltration components.

[0042] Downstream of the deionization resin bed 32 is a deionization bedrestraint 34 and a terminal filter element 36, in sequence. Therestraint 34 preferably comprises the same polypropylene mesh utilizedfor the illustrated depth filter 26 and carbon bed restraint 30. Theresin bed restraint 34 serves to prevent passage of deionization bedfragments or fines, as well as any other particulates that have escapedthe upstream filters 26, 30. The restraint 34 also serves to protect thefilter element 36 downstream of the restraint 34.

[0043] The terminal filter element 36 consists of a 0.2 micron or finermicro- to ultra-filtration membrane, chemically treated to incorporate aquaternary amine exchanger to bind endotoxins. Alternatively, theterminal filter can comprise a 0.2 micron or finer filter along with asecond membrane having enhanced endotoxin binding characteristics. Suchendotoxin binding membranes are available under the trade name HP200from the Pall Specialty Materials Co. The terminal filter 36 thusremoves endotoxins, as well as microbes and particulate matter of lessthan 1 micron, from water passing therethrough. Desirably, the porositycan be as low as a 10,000 molecular weight cutoff, sufficient to filtermany viruses.

[0044] Water passing through the pack 12 and exiting the housing outlet24 conforms to the water quality standards set forth in the U.S.Pharmacopoeia procedures for “Sterile Water for Injection,” as notedabove.

[0045] Desirably, the water purification pack 12 includes an upstreamcap 38 over the housing inlet 22, and a downstream cap 40 over thehousing outlet 24. The sterility of the purification elements housedwithin the housing 20 are thus maintained until use. As will beunderstood in the art, the inlet 12 and outlet 24 can be provided withthreads or Luer-type fittings to mate with upstream and downstreamelements in the peritoneal dialysate delivery system 10 (FIG. 1).

[0046] A similar water purification pack is described at Col. 7, line 19to Col. 8, line 24 of U.S. Pat. No. 5,725,777, entitled Reagent/DrugCartridge, the disclosure of which is incorporated herein by reference.

[0047] Single-Bed Reagent Cartridge

[0048] FIGS. 3-5 illustrate a single-bed reagent cartridge 14,constructed in accordance with a first embodiment. The figuresillustrate various stages of dissolution, as will be better understoodfrom the methods of operation discussed hereinbelow.

[0049]FIG. 3 shows a fully charged reagent cartridge 14, in accordancewith the first embodiment. The cartridge 14 comprises rigid walledhousing 50 with an inlet port 52 at an upstream end, and an outlet port54 at a downstream end. Within the housing, a number of porous elementsdefine a fluid flow path between the inlet port 52 and the outlet port54.

[0050] The housing 50 is preferably transparent or translucent,advantageously enabling the user to observe the operation of the deviceand complete dissolution of reagents prior to use of a producedsolution, as will be apparent from the discussion of the method ofoperation, discussed hereinbelow. Examples of translucent andtransparent polymers are polypropylene, polycarbonate and many otherwell-known materials.

[0051] Within the housing 50, immediately downstream of the inlet port52, is an inlet frit 56, which serves as a safety filter to contain anyreagent which escapes the restraints described below. An outlet frit 58serves a similar function immediately upstream of the outlet 54.Desirably, the inlet frit 56 and the outlet frit 58 comprise porouselements having a porosity smaller than the smallest particle of thereagents housed within the cartridge 14. The frits 56, 58 thus serve asfilters to ensure that no reagent escapes the cartridge prior todissolution, as will be described below. An exemplary frit is amultilayered polypropylene laminate, having a porosity between about 1μm and 100 μm, more preferably between about 10 μm to 50 μm. Furtherdetails on the preferred material are given below, with respect to thereagent restraints.

[0052] Downstream of the inlet frit 56 is an upstream reagentcompression component 60. Similarly, upstream of the outlet frit 58 is adownstream reagent compression component 62. The compression components60, 62 preferably comprise materials which have sponge-like elasticityand, as a result of compression, exert axial pressure while trying toreturn to its original, expanded form. The compression components 60, 62preferably comprise compressible, porous, open cell polymer or foam,desirably more porous than the frits, to avoid generation of backpressure. An exemplary material for the compression components is apolyurethane foam. Desirably, the compression components 60, 62 andsurrounding housing 50 are arranged such that the compression components60, 62 exert a compressive force on the reagent bed regardless of thesize of the reagent bed. In other words, the compression components 60and 62 would, if left uncompressed, together occupy a greater volumethan that defined by the housing 50. Desirably, the pressure exerted isbetween about 50 psi and 500 psi, more preferably between about 100 psiand 300 psi.

[0053] It will be understood that, in other arrangements, metal orpolymer coiled springs and porous plates can serve the same function.Such alternative compression components are disclosed, for example, withrespect to FIGS. 12-15; Col. 9, lines 8-53 of U.S. Pat. No. 5,725,777,the disclosure of which is incorporated herein by reference. It willalso be understood, in view of the discussion below, that a singlecompression component can serve the function of the illustrated twocompression components. Two components exerting pressure on either sideof a reagent bed 64 (described below), however, has been foundparticularly advantageous in operation.

[0054] A single reagent bed 64 is situated between the compressioncomponents 60, 62. The reagent bed 64 is desirably sandwiched between anupstream reagent restraint 66 and a downstream reagent restraint 68. Theupstream reagent restraint 66 is thus positioned between the reagent bed64 and the upstream compression component 60, while the downstreamreagent restraint 68 is positioned between the reagent bed 64 and thedownstream compression component 62.

[0055] The restraints 66, 68 desirably prevent the passage of reagentparticles in their dry formulation. The porosity of the restraints istherefore selected to be less than the size of the smallest particleswithin the reagent bed, depending upon the particular reagentformulations and physical particle size desired. Desirably, the poresare large enough to avoid excessive pressure drop across the restraints.Preferably, the restraint porosity in the range between about 1 μm and100 μm, more preferably between about 10 μm to 50 μm. An exemplaryrestraint, suitable for the illustrated peritoneal dialysis application,comprises the same material as the frits 56, 58, and consists of anon-woven polymer, particularly polypropylene with a porosity of about20 microns. Another exemplary restraint comprises sintered polyethylenewith a porosity of about 30 microns.

[0056] Additionally, the restraints 66, 68 are sized and shaped toextend completely across the housing 50, forming an effective sealagainst reagent particulates escaping around the restraints 66, 68.

[0057] In the illustrated embodiment, the reagent bed 64 comprises acomplete formulation of dry or lyophilized reagents required to producea peritoneal dialysis solution. In the illustrated single-bedembodiment, the reagent bed 65 is a mixture of compatible reagents, suchas will not exhibit spontaneous chemical reaction from prolonged contactin their dry form. Accordingly, a buffering agent such as an acetate orlactate, and particularly sodium lactate, is employed in place of abicarbonate. Further reagents include electrolytes, such as sodiumchloride, magnesium chloride, potassium chloride and calcium chloride; asugar, preferably dextrose; and an acid, particularly citric acid.Advantageously, the acid component of the reagent bed 65 can be lowerthan conventional solutions, since storage in dry form alleviates thetendency for dextrose caramelization.

[0058] The illustrated housing 50 holds reagents sufficient to produce 2liters of a typical peritoneal dialysate solution. Accordingly, thereagent bed 64 holds the following reagents: TABLE I Dry ReagentConstituents Mass Dry Volume Calcium chloride 514 mg NegligibleMagnesium chloride 101.6 mg Negligible Sodium lactate 8.96 g 24 mLSodium chloride 10.76 g 22 mL Dextrose 50 g 70 mL Total 70 g 101 mL 

[0059] The dry volume of the above-listed reagents, which can produce 2L of 2.5% dextrose peritoneal dialysate, is thus about 100 mL. Thehousing 50 for such a formulation need only be about 125% to 500% of thedry reagent volume, more preferably about 150% to 200%, depending uponthe selected compression components 60, 62. The illustrated housing 50is about 2″ in diameter and about 3″ in height, thus occupying about 175mL. The cartridge 14 thus represents a much smaller and more stable formof dialysate for storage and transport, compared to 2 L of preparedsolution. If a smaller or larger volume of solution is desired, theskilled artisan can readily determine the proportionate weight andvolume of dry reagents required in the reagent bed 64, such as forproducing 1 L, 3 L, 6 L, 10 L, etc. Similarly, the skilled artisan canreadily determine the proportions of reagents desirable for 1.5%dextrose dialysate, 4% dextrose dialysate, etc.

[0060] The housing inlet port 52 and outlet port 54 are covered by aninlet port cover 70 and an outlet port cover 72, respectively. The portcovers 70, 72 advantageously seal out moisture and preventdestabilization of the dry reagents housed within during transport andstorage. As with the water purification pack, the inlet port 52 andoutlet port 54 can be configured with threaded or Luer-type connectionfittings. In the illustrated embodiment, the inlet port 52 is configuredto mate with the outlet 24 of the water purification pack 12 (FIG. 2),while the outlet port 54 is configured to mate with the downstream tube18 (see FIG. 1).

[0061] Double-Bed Reagent Cartridge

[0062]FIGS. 6 and 7 illustrate a double-bed reagent cartridge 14′,constructed in accordance with a second embodiment FIGS. 6 and 7illustrate the cartridge 14′ in fully charged and fully depletedconditions, respectively, as will be better understood from the methodsof operation discussed hereinbelow.

[0063] With reference initially to FIG. 6, the housing 50 of thedouble-bed reagent cartridge 14′ is preferably similar to that of thefirst embodiment, such that like reference numerals are used to refer tolike parts. Thus, the housing 50 defines an inlet port 52 and outletport 54, and contains porous elements between the inlet port 52 andoutlet port 54, such as to define a fluid flow path through the housing50. Specifically, the housing 50 contains an upstream frit 56, upstreamcompression component 60, upstream reagent restraint 66, downstreamreagent restraint 68, downstream compression component 62 and downstreamfrit 58. Each of these elements can be as described with respect to theprevious embodiment.

[0064] Unlike the single-bed cartridge 14 of FIGS. 3-5, however,multiple reagent beds are confined between the upstream restraint 66 anddownstream restraint 68. In particular, a primary reagent bed 80 and asecondary reagent bed 82 are shown in the illustrated embodiment,separated by at least one restraint. In the illustrated embodiment, thereagent beds 80 and 82 are separated by a first intermediate restraint84 and second intermediate restraint 86, as well as an intermediatecompression component 88 between the intermediate restraints 84 and 86.

[0065] Accordingly, the primary reagent bed 80 is confined betweenupstream restraint 66 and the first intermediate restraint 84, while thesecondary reagent bed 84 is similarly confined between the secondintermediate restraint 86 and the downstream restraint 68. Theintermediate reagent bed restraints 84, 86 desirably serve to containthe reagents within the beds 80, 82 in their dry form, while still beingporous enough to allow diluent, along with any dissolved reagents, topass through. Accordingly, the intermediate reagent restraints 84, 86can have the same structure as the frits 56, 58 and upstream anddownstream reagent restraints 66, 68, as described above with respect tothe single-bed embodiment. Similarly, the intermediate compressioncomponent 88 can have the same structure as the upstream and downstreamcompression components 60, 62.

[0066] Each of the intermediate compression component 88 and theintermediate reagent restraints 84, 86 are interposed between andseparate the primary reagent bed 80 from the second reagent bed 82. Dueto the selected porosity of the elements, particularly the intermediaterestraints 84, 86, constituents of the two reagent beds 80, 82 thereforedo not interact with one another in their dry states.

[0067] The illustrated double-bed embodiment therefore enables separatestorage of different reagents within the same housing 50. A completeformulation of the dry reagents required to produce a peritonealdialysis solution may contain reagents that react undesirably whenexposed to one other for prolonged periods of time, in either dry orliquid forms, as noted in the Background section. For example,bicarbonates are preferred, physiologically compatible buffering agentsfor peritoneal dialysis, but tend to be very reactive with typical saltsin the dialysate formulation, such as calcium chloride or magnesiumchloride. The reactions form insoluble calcium carbonate or magnesiumcarbonate, and also liberate CO₂. Because of the potential reactivity ofincompatible reagents, it is preferable to separately store thesereagents within the device housing 50.

[0068] Separate storage is accomplished by separating reagents intocompatible groupings, which are then placed in separate compartmentswithin the housing. The compartments are represented, in the illustratedembodiment, by the primary reagent bed 80 and the secondary reagent bed82. The potentially reactive reagents are thereby constrained frommovement through the housing, when maintained in their dry form, byreagent bed restraints 66, 84, 86, 68 at the upstream and downstreamends of each of the reagent beds 80, 82. As noted above, the reagent bedrestraints 66, 84, 86, 68 have fine enough porosity to prevent thepassage of reagent particles in their dry form.

[0069] In the illustrated embodiment, the primary reagent bed 80 is areagent mixture, preferably comprising: electrolytes, particularlysodium chloride, potassium chloride, calcium chloride and magnesiumchloride; a sugar, particularly dextrose. In other arrangements, theprimary reagent bed 80 can also comprise a buffer.

[0070] The secondary reagent bed 82 can contain at least one componentwhich is unstable in the presence of at least one component in theprimary reagent bed 80. Advantageously, the secondary reagent bed 82contains a bicarbonate, such as sodium bicarbonate. Because thebicarbonate is separated from calcium chloride and magnesium chloride,the reagents do not react to form insoluble precipitates.

[0071] The skilled artisan will readily appreciate that, in otherarrangements, the primary reagent bed 80 can contain the bicarbonate ifthe secondary bed 82 contains calcium chloride and/or magnesiumchloride. In still other alternatives, other incompatible reagents formedical solutions can be similarly separated into reagent beds withinthe same housing. Moreover, three or more reagent beds can be utilizedto separate multiple incompatible reagents.

[0072] The illustrated housing 50 holds reagents sufficient to produce 2liters of a typical peritoneal dialysate solution. Accordingly, thereagent beds 80, 82 hold the following reagents: TABLE II PrimaryReagent Bed Mass Dry Volume Calcium chloride 514 mg negligible Magnesiumchloride 101.6 mg negligible Sodium chloride 10.76 g 22 mL Dextrose 50 g70 mL Subtotal 61 92 mL Secondary Reagent Bed Sodium bicarbonate 6.64 g61 mL Total 68 g 98 mL

[0073] The dry volume of the above-listed reagents, which can produce 2L of 2.5 % dextrose peritoneal dialysate, is thus about 98 mL. As withthe previously described single-bed embodiment, the total volume of thecartridge 14′ is preferably between about 125% and 500%, and morepreferably 150% and 200%, of the dry reagent volume. As also notedabove, the skilled artisan can readily determine the proportionateweights and volumes of dry reagents required for forming otherperitoneal dialysate solutions, such as 1.5% dextrose dialysate, 4%dextrose dialysate, etc.

[0074] Notably, the double-bed cartridge utilizes bicarbonate as thebuffer, and omits the need for physiologically damaging acid by enablingproduction of a physiologic solution.

[0075] Method of Operation

[0076] In operation, purified diluent is provided to a reagent cartridge14 or 14′, which is fully charged with an appropriate amount of dryreagent, as set forth above. Diluent may comprise filtered andde-ionized water that is independently provided at the point ofadministration. It will be understood that other physiologicallycompatible diluents can also be employed. In the preferred embodiment,however, available water (e.g., municipal tap water) is provided to thesystem 10 of FIG. 1, such that the purified diluent is produced on siteand need not be produced remotely and transported, significantlyreducing the cost of transportation.

[0077] Accordingly, with reference to FIG. 2, diluent in the form ofavailable potable water is first provided to water purification pack 12of FIG. 2. Pressures commonly found in municipal water systems issufficient to feed the water through the purification pack 12.Alternatively, a hand pump or large syringe can be supplied with ameasured volume of water, and water hand pumped therefrom into thepurification pack 12.

[0078] The diluent enters the inlet 22 and passes through depth filter26, where particulates larger than about 1 micron are filtered out.Filtered diluent continues downward through granular carbon bed 28,where residual organics such as endotoxins and additives such aschlorine, chloramine and trihalomethanes are absorbed. After beingadditionally filtered by carbon bed restraint 30, the partially purifieddiluent passes into deionization resin bed 32. Dissociated ions andother charged particulates in solution bind to the resins. Endotoxinswhich have escaped the upstream components are also retained in theresin bed 32. After passing through the resin bed restraint 34, whichretains the contents of the resin bed 34, the diluent is furtherfiltered through the terminal filter element 36. This filter 36 has avery fine porosity (e.g., about 0.2 micron or finer), and includeschemical treatment with a quaternary amine exchanger for bindingresidual endotoxins.

[0079] The multiple filtration and chemical binding components of thewater purification pack 12 thus ensure removal of particulate, ionic andorganic contaminants from the diluent as it passes through the pack 12.Endotoxins, including organic matter such as cell walls from deadbacteria, can be particularly toxic. Highly purified diluent, sufficientto comply with the water quality standards of the U.S. pharmacopoeia for“sterile water for injection,” exits the outlet 24. With reference toFIG. 1 again, purified diluent then passes from the water purificationpack 12 to the reagent cartridge 14.

[0080] FIGS. 3-5 illustrate dissolution of dry reagent 64 as diluentpasses through the single-bed reagent cartridge 14 of the firstembodiment. While illustrated cross-sectionally, it will be understoodthat the preferred transparent or translucent housing 50 enables theuser to similarly observe dissolution of the reagent bed 64 as solventor diluent passes therethrough. Additionally, the user can observewhether insoluble precipitates are present within the reagent bed, priorto employing the cartridge 14. Advantageously, gravitational force issufficient to draw the water through the cartridge 14.

[0081] Referring initially to FIG. 3, purified diluent enters thecartridge 14 through the inlet port 52. Preferably, purified diluent isfed directly from the water purification pack 12. “Directly,” as usedherein, does not preclude use of intermediate tubing, etc, but ratherrefers to the fact that water is purified on site immediately prior tosolution formation, rather remotely produced and shipped. It will alsobe understood, however, that the illustrated reagent cartridge will haveutility with other sources of sterile diluent.

[0082] The diluent passes through the porous inlet frit 56 and theupstream compression component 60. In the illustrated embodiment, thecompression component 60 is a porous, open-celled foam, which readilyallows diluent to pass therethrough. The diluent then passes through theupstream reagent restraint 66 to reach the dry reagent bed 64. Inaddition to retaining the dry reagents in the bed 64, the frit 56 andrestraint 66 facilitate an even distribution of water flow across thesectional area of the housing 50.

[0083] As the solution passes through interstitial spaces in the bed 64,the dry reagents are erroded, preferably dissolved, and carried by thediluent through the downstream reagent restraint 68, the downstreamcompression component 44 and the outlet frit 58, exiting through outlet24. The solution passes through the tube 18 into the collectionreservoir 16 (see FIG. 1) or directly into the peritoneal cavity of apatient.

[0084] Referring to FIG. 4, as the reagents are dissolved, the volume ofthe reagent bed 64 is reduced, as can be seen from a comparison of FIG.4 with FIG. 3. The compression components 60, 62 apply continuouscompressive force on either side of the reagent bed 64. As dry reagentis dissolved, the compressive force packs the reagents close together.Such continuous packing prevents expansion of interstitial spaces as thereagent particles are dissolved. Without the compressive force, theinterstitial spaces between the reagent particles tend to expand intolarger channels within the reagent bed 64. These channels would serve asdiluent flow paths, which would permit a large volume of diluent to flowthrough the bed 64 with minimal further dissolution. Significantportions of the bed would be by-passed by these channels, anddissolution would be slow and inefficient. Applying continuouscompression to the beds minimizes this problem by continuously forcingthe reagent particles together as the bed dissolves, ensuringcontinuous, even exposure of the diluent to the reagents of the bed 64.

[0085] Though two compression components 60, 62 are preferred, thuscompressing the reagent bed 64 from two sides, it will be understoodthat a single compression component can also serve to keep the regentbeds 64 compacted. Moreover, though illustrated in an axial arrangement,such that diluent flows through the compression components 60, 62, itwill be understood that the compression components can exert a radialforce in other arrangements.

[0086] The compressive force of the preferred compression components 60,62, exerted evenly across the housing 50, additionally aids inmaintaining the planar configuration of the reagent restraints 66, 68 oneither side of the reagent bed 64, even as the compression components60, 62 move the restraints inwardly. The restraints 66, 68 thus continueto form an effective seal against the housing sidewalls, preventing dryreagent particulates from escaping the bed 64 until dissolved.

[0087] With reference to FIG. 5, dissolution continues until the reagentbed is depleted and the restraints 66, 68 contact one another. Diluentcan continue to flow through the housing 50 into the reservoir 16(FIG. 1) until the appropriate concentration of peritoneal dialysatesolution is formed. For example, in the illustrated embodiment, 2 litersof diluent should be mixed with the contents of the reagent bed 64.Accordingly, 2 liters of diluent are passed through the housing 50. Thecontents are typically fully dissolved by the time about 1.5 liters haspassed through the housing, but diluent can continue to flow until theappropriate final concentration is reached in the reservoir.Alternatively, a concentrate can be first formed and independentlydiluted.

[0088] Advantageously, the illustrated apparatus and method can formperitoneal dialysis solution simply by passing water through thecartridge 50, without complex or time consuming mixing equipment. Thesolution can thus be formed on-site, immediately prior to delivery tothe peritoneal cavity, such that the dialysate need not be shipped orstored in solution form. Accordingly, a low acid level is possiblewithout undue risk of dextrose carmelization. Conventionally, apre-formed dialysis solution formed has a pH between about 4.0 and 6.5,and the exemplary reagent mix of Table I produces a conventionalsolution with pH of about 5.2. Solution produced from the illustratedsingle-bed cartridge of FIGS. 3-4, however, can have lower acidity,since dextrose does not sit in solution for extended periods of time.Accordingly the pH level is preferably between about 6.0 and 7.5, morepreferably about 7.0.

[0089] Referring to FIGS. 6 and 7, the double-bed reagent cartridge 14′operates in similar fashion. Purified diluent is fed to the housinginlet 52, and passes through the inlet frit 56, the upstream compressioncomponent 60, the upstream restraint 66, and into the primary reagentbed 80. Dissolution of reagents in the primary bed 80 forms a solutionwhich passes on through the first intermediate restraint 84, theintermediate compression component 88 and the second intermediaterestraint 86. Reagents in the secondary bed 82 then also dissolve intothe diluent, and the enriched solution continues on through thedownstream reagent restraint 68, the downstream compression component 62and the outlet frit 58. A complete solution thus exits the outlet port54.

[0090] As in the previous embodiment, the regent beds 80, 82 arecontinually compressed as the reagents dissolve. Use of threecompression components 60, 88, 62 has been found to improve dissolutionby compressing each bed 80, 82 from two sides. The skilled artisan willunderstand, however, that two compression components, in the positionsof the upstream and downstream third components, can adequately serve tokeep the reagent beds compressed enough to aid the rate of dissolution,particularly if provided with a high degree of elasticity. Similarly, asingle intermediate compression component, in the position of theillustrated intermediate compression component 88, can accomplish thisfunction, while advantageously also separating the incompatible reagentbeds. Additionally, the compression component need not be axiallyaligned with the reagent beds, but could instead surround or besurrounded by the reagent beds, in which case the compression componentswould preferably be outside the diluent flow path.

[0091] Advantageously, the illustrated embodiments provide stable, dryforms of peritoneal dialysis solutions. Storage and transport of thereagent cartridges of the illustrated embodiments representsconsiderable cost savings over storage and transport of preparedperitoneal dialysate solutions. Dry or lyophilized reagents are moreovermore stable than solution, and therefore less harmful to the patient.

[0092] While the storage and transport of dry reagents is generallyrecognized as advantageous, practical application has been difficult.The described embodiments not only provide transport and storage, butadditionally provide integrated mechanisms to ensure completedissolution of the dry reagents. Continuous compression of the reagentbed(s) during dissolution, combined with the transparent windowsallowing real time viewing of the dissolution, ensure rapid, completeand verifiable dissolution of the reagents. Thus, the preferredembodiments can be utilized on site, even in the home, without requiringcomplex mixing and/or analytical tools.

[0093] Moreover, the illustrated embodiments facilitate a widerpracticable range of reagents. For example, physiologically compatiblebicarbonate can be employed along with calcium and magnesium. Separatestorage and solution preparation only immediately prior toadministration enables this combination. High dextrose solutions, asappropriate for peritoneal dialysis, can be employed without acidicbuffers, such that physiologically compatible pH levels can bepractically obtained, preferably between about 4.0 and 7.5, and morepreferably between about 6.0 and 7.5. The reagents listed in Table IIproduce a solution with a pH of about 7.0.

[0094] Additionally, the preferred arrangement includes a waterpurification pack 12, obviating transport of sterile diluent. Thus, thebulk of peritoneal dialysis solution can be provided through tap waterat the site of peritoneal dialysis administration. Potable water ispurified through the water purification pack, and thus purified waterfed through a reagent cartridge. Simply by gravitational action, waterflow through the cartridge results in complete dissolution of dryreagents and produces a complete solution suitable for peritonealdialysis.

[0095] Although the foregoing invention has been described in terms ofcertain preferred embodiments, other embodiments will become apparent tothose of ordinary skill in the art in view of the disclosure herein.Accordingly, the present invention is not intended to be limited by therecitation of preferred embodiments, but is intended to be definedsolely by reference to the dependent claims.

What is claimed is:
 1. An apparatus for producing a peritoneal dialysissolution comprising: a housing defining a fluid flow path therethrough;and at least one reagent bed within the housing along the fluid flowpath, wherein the at least one reagent bed comprises dry reagentsforming at least a part of a solution for peritoneal dialysis, whereinthe reagent bed contains different reagents.
 2. The apparatus of claim1, further comprising a compression component adjacent the at least onereagent bed.
 3. The apparatus of claim 2, wherein the compressioncomponent comprises a compressible foam member.
 4. The apparatus ofclaim 2, wherein the compression component is positioned within thefluid flow path, and comprises an open cell compressible foam member. 5.The apparatus of claim 2, wherein the compression component comprises acoiled spring.
 6. The apparatus of claim 2, wherein the at least onereagent bed is compressed between an upstream compression component anda downstream compression component.
 7. The apparatus of claim 6, whereinthe at least one reagent bed is confined between an upstream reagentrestraint, positioned between the upstream compression component and theat least one reagent bed, and a downstream reagent restraint, positionedbetween the downstream compression component and the at least onereagent bed.
 8. The apparatus of claim 6, wherein the at least onereagent bed includes dry forms of electrolyte salts, dextrose, and abuffer.
 9. The apparatus of claim 6, wherein the at least one reagentbed comprises a first reagent bed and a second reagent bed.
 10. Theapparatus of claim 9, wherein the first reagent bed is downstream of thesecond reagent bed.
 11. A system for producing at least part of aperitoneal dialysis solution, comprising: a reagent cartridge having afluid inlet and a fluid outlet defining a flow path therethrough, thereagent cartridge housing at least one dry reagent bed along the fluidflow path and at least one compression component exerting continualpressure on the at least one dry reagent bed; and a water purificationpack configured to connect upstream of the reagent cartridge, the waterpurification pack housing filters, activated carbon and ion exchangeresins such as to convert potable water to injectable quality water. 12.The system of claim 11, wherein the cartridge includes dry reagentssufficient to produce a complete formulation of peritoneal dialysissolution.
 13. The system of claim 12, wherein the at least one reagentbed includes dry reagents suitable for forming 2 liters of peritonealdialysis solution.
 14. The system of claim 12, wherein the reagent bedincludes dry reagents suitable for forming 2.5% dextrose peritonealdialysis solution.
 15. The apparatus of claim 11, wherein the at leastone reagent bed comprises a first reagent bed and a second reagent bed.16. The apparatus of claim 15, wherein the first reagent bed isdownstream of the second reagent bed.